title: Acetylcholine-induced vasodilatation in the human peripheral circulation is independent of ATP-sensitive K+ channels and prostacyclin.
abstract: BACKGROUND
  Both experimental and clinical studies have shown that the increase in regional blood flow induced by acetylcholine is not completely prevented by inhibitors of the synthesis of endothelium-derived nitric oxide. To establish the role of ATP-sensitive potassium (KATP) channels and prostacyclin in mediating acetylcholine-induced increase in peripheral blood flow in humans, we assessed the effects of acetylcholine on the iliac artery blood flow velocity before and after glibenclamide, an antagonist of KATP channels, or before and after acetylsalicylic acid, an inhibitor of prostacyclin production.
  
  
  METHODS
  Seventeen patients without evidence of peripheral vascular disease and normal coronary arteries at angiography received intra-iliac incremental bolus injections of acetylcholine (0.2, 2, 20 and 50 micrograms) via a 5F femoral sheath, at the end of routine cardiac catheterization. All injections were repeated 90 minutes after oral administration of glibenclamide (10 mg) in 10 patients of 15 minutes after i.v. infusion of acetylsalicylic acid (1000 mg) in the remaining 7 patients. Right iliac artery blood flow velocity was measured by using an intravascular 0.014-in Doppler guidewire.
  
  
  RESULTS
  Before glibenclamide or acetylsalicylic acid administration, acetylcholine infusion increased average peak velocity by 128% (p < 0.001) and by 121% (p < 0.001), respectively. After glibenclamide or acetylsalicylic acid the increases of average peak velocity during acetylcholine infusion (by 121%, p < 0.001, and by 121%, p < 0.001, respectively) were similar (p = ns) to those observed during the control infusion.
  
  
  CONCLUSIONS
  In man acetylcholine-induced vasodilatation in the territory supplied by the iliac artery is not prevented by glibenclamide or acetylsalicylic acid, thus suggesting that it is independent of activation of KATP channels and prostacyclin release.
authors.affiliation: Servizio Speciale di Diagnosi e Cura di Emodinamica, Universitá di Roma Tor Vergata European Hospital.
authors.forename: F
authors.initials: F
authors.lastname: Tomai
authors.forename: F
authors.initials: F
authors.lastname: Crea
authors.forename: A
authors.initials: A
authors.lastname: Gaspardone
authors.forename: F
authors.initials: F
authors.lastname: Versaci
authors.forename: A S
authors.initials: AS
authors.lastname: Ghini
authors.forename: A
authors.initials: A
authors.lastname: Parma
authors.forename: L
authors.initials: L
authors.lastname: Chiariello
authors.forename: P A
authors.initials: PA
authors.lastname: Gioffré
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000502:physiology; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D000109:Acetylcholine; D001241:Aspirin; D005905:Glyburide